title: Keloid-derived keratinocytes exhibit an abnormal gene expression profile consistent with a distinct causal role in keloid pathology.
abstract: Keloids are disfiguring scars that extend beyond the original wound borders and resist treatment. Keloids exhibit excessive extracellular matrix deposition, although the underlying mechanisms remain unclear. To better understand the molecular basis of keloid scarring, here we define the genomic profiles of keloid fibroblasts and keratinocytes. In both cell types, keloid-derived cells exhibit differential expression of genes encompassing a diverse set of functional categories. Strikingly, keloid keratinocytes exhibited decreased expression of a set of transcription factor, cell adhesion, and intermediate filament genes essential for normal epidermal morphology. Conversely, they exhibit elevated expression of genes associated with wound healing, cellular motility, and vascular development. A substantial number of genes involved in epithelial-mesenchymal transition were also up-regulated in keloid keratinocytes, implicating this process in keloid pathology. Furthermore, keloid keratinocytes displayed significantly higher migration rates than normal keratinocytes in vitro and reduced expression of desmosomal proteins in vivo. Previous studies suggested that keratinocytes contribute to keloid scarring by regulating extracellular matrix production in fibroblasts. Our current results show fundamental abnormalities in keloid keratinocytes, suggesting they have a profoundly more direct role in keloid scarring than previously appreciated. Therefore, development of novel therapies should target both fibroblast and keratinocyte populations for increased efficacy.
authors.affiliation: Research Department, Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio 45229, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Hahn
authors.forename: Kathryn
authors.initials: K
authors.lastname: Glaser
authors.forename: Kevin L
authors.initials: KL
authors.lastname: McFarland
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Steven T
authors.initials: ST
authors.lastname: Boyce
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Supp
mesh_terms: D000293:Adolescent; D000328:Adult; D002448:Cell Adhesion / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007627:Keloid / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D059467:Transcriptome; D015854:Up-Regulation; D055815:Young Adult